Fetal Window of Vulnerability to Airborne Polycyclic Aromatic Hydrocarbons on Proportional Intrauterine Growth Restriction

Hyunok Choi,Frederica P Perera,Xihong Lin,Lu Wang,John D Spengler,Alex R Cook

doi:10.1371/journal.pone.0035464

Abstract

BackgroundAlthough the entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters.MethodsIn a group of healthy, non-smoking pregnant women with no known risks of adverse birth outcomes, personal exposure to eight airborne PAHs was monitored once during the second trimester for the entire cohort (n = 344), and once each trimester within a subset (n = 77). Both air monitoring and self-reported PAH exposure data were used in order to statistically estimate PAH exposure during the entire gestational period for each individual newborn.ResultsOne natural-log unit increase in prenatal exposure to the eight summed PAHs during the first trimester was associated with the largest decrement in the Fetal Growth Ratio (FGR) (−3%, 95% Confidence Interval (CI), −5 to −0%), birthweight (−105 g, 95% CI, −188 to −22 g), and birth length (−0.78 cm, 95% CI, −1.30 to −0.26 cm), compared to the unit effects of PAHs during the subsequent trimesters, after accounting for confounders. Furthermore, a unit exposure during the first trimester was associated with the largest elevation in Cephalization Index (head to weight ratio) (3 μm/g, 95% CI, 1 to 5 μm/g). PAH exposure was not associated with evidence of asymmetric growth restriction in this cohort.ConclusionPAH exposure appears to exert the greatest adverse effect on fetal growth during the first trimester. The present data support the need for the protection of pregnant women and the embryo/fetus, particularly during the earliest stage of pregnancy.

Highlights

Polycyclic aromatic hydrocarbons (PAHs) are multiphasic fused aromatic rings of carbon compounds
Considering both biological and epidemiological evidence, we tested the hypothesis that an embryo/fetus is most vulnerable during the first trimester per unit polycyclic aromatic hydrocarbons (PAHs) exposure, compared to a comparable unit of exposure during the second or the third trimester in a cohort of non-smoking, healthy pregnant women. We examined this by 1) using a newly developed model to estimate personal exposure to airborne PAHs during the entire gestational period for each newborn; 2) comparing the birth outcome effect sizes per unit PAH exposure during given window of interest to those during other periods, including the sixth gestational month as the reference period; 3) examining whether the gestational period of IUGR onset is associated with an IUGR subtype as well as its severity
The severity of Fetal Growth Ratio (FGR) was inversely correlated with the Cephalization Index (Pearson’s coefficient = 20.68, p-value,0.001)

Summary

Introduction

Polycyclic aromatic hydrocarbons (PAHs) are multiphasic fused aromatic rings of carbon compounds. Some PAHs are potent mutagens, genotoxins and known human carcinogens [4]. In utero exposure of mice to benzo[a]pyrene (B[a]P) and dibenzo[a,l]pyrene could induce the formation of DNAadducts in thymocytes and splenocytes of the offspring [7]. Such adducts are vital precursors to PAH-mediated carcinogenesis [7]. The entire duration of fetal development is generally considered a highly susceptible period, it is of public health interest to determine a narrower window of heightened vulnerability to polycyclic aromatic hydrocarbons (PAHs) in humans. We posited that exposure to PAHs during the first trimester impairs fetal growth more severely than a similar level of exposure during the subsequent trimesters

Methods

Results

Discussion

Conclusion